This is an open-label non-randomized phase I/II feasibility study to treat patients with high-risk leukemia with HA-1 TCR
transduced virus-specific donor-derived T-cells 8 and 14 weeks after allo-SCT.
The HA-1 TCR transduced virus-specific T-cells will be generated from donor leukocytes obtained from a leukapheresis product of the stem cell donor. Minimally one and maximally two CMV- and/or EBV-specific T cell populations will be isolated from PBMC using Streptamers. After 2-3 days of culture, virus-specific T-cells are transduced with a retroviral vector encoding the HA-1-TCR. After 8-12 days of additional culturing, the transduced virus-specific T-cells will be analyzed for virus-specific T-cell purity and HA-1-TCR cell surface expression using virus- and HA-1-specific tetramers. For release of the HA-1-TCR transduced virus-specific T-cells, ¡Ý 95% of the cell product must be T-cells, ¡Ý 60% of T-cells must be antigen-specific as measured with tetramers specific for the endogenous virus-TCR and introduced HA-1-TCR, and ¡Ý5% of lymphocytes must be HA-1-tetramer positive. The maximal amount of virus- or HA-1-tetramer negative T-cells with unknown specificity administered in the T-cell product is <0.3 x 106 cells/kg body weight in patients transplanted with HLA-matched related donors and <0.15 x 106 cells/kg body weight in patients transplanted with unrelated donors or HLA-A2 mismatched donors.